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The beta2 but not alpha7 subunit of the nicotinic acetylcholine receptor is required for nicotine-conditioned place preference in mice.

RATIONALE: Tobacco use is implicated in approximately 440,000 deaths per year, making it the leading cause of preventable death in the United States. Although it is generally recognized that tobacco use is correlated with a variety of health-related complications, many smokers are unsuccessful in their efforts to stop smoking using current cessation therapies. OBJECTIVES: Given that nicotine is the addictive component of tobacco, successful smoking cessation therapies must address the various processes, including reward, which contribute to nicotine addiction. As such, determining the nicotinic receptor subtypes involved in nicotine reward is of utmost importance to understanding how nicotine addiction progresses. METHODS: Conditioned place preference (CPP) in three-chamber conditioning boxes was performed. For antagonist studies, drug was given on all conditioning sessions 10 min before nicotine or saline injection and placement in the boxes. RESULTS: We have demonstrated that a pretreatment with the alpha4beta2 subunit of the nicotinic acetylcholine receptor (nAChR) antagonist dihydro-beta-erythroidine (2.0 mg/kg, s.c.) blocked nicotine (0.5 mg/kg, s.c.) CPP in wild-type mice (C57BL/6 mice). In contrast, pretreatment with an antagonist of the alpha7 subunit of the nAChR, methyllycaconitine (MLA, 5.0 or 10.0 mg/kg, s.c.), had no effect on this behavior. Finally, we showed that mice lacking the beta2 subunit of the nAChR did not exhibit nicotine CPP while alpha7 knock-out mice did. CONCLUSION: Taken together, these data suggest that the beta2 subunit of the nAChR is critically involved in nicotine reward as measured by CPP.

Aconitine↗

Issues in the classification of multimodal communication signals.

Communication involves complex behavior in multiple sensory channels, or "modalities." We provide an overview of multimodal communication and its costs and benefits, place examples of signals and displays from an array of taxa, sensory systems, and functions into our signal classification system, and consider issues surrounding the categorization of multimodal signals. The broadest level of classification is between signals with redundant and nonredundant components, with finer distinctions in each category. We recommend that researchers gather information on responses to each component of a multimodal signal as well as the response to the signal as a whole. We discuss the choice of categories, whether to categorize signals on the basis of the signal or the response, and how to classify signals if data are missing. The choice of behavioral assay may influence the outcome, as may the context of the communicative event. We also consider similarities and differences between multimodal and unimodal composite signals and signals that are sequentially, rather than simultaneously, multimodal.

Animal Communication↗

Establishing and maintaining treatment effects with less intrusive consequences via a pairing procedure.

The generality and long-term maintenance of a pairing procedure designed to improve the efficacy of less intrusive procedures were evaluated for the treatment of problem behavior maintained by automatic reinforcement exhibited by 2 individuals with developmental disabilities. Results suggested that a less intrusive procedure could be established as a conditioned punisher by pairing it with an effective punisher contingent on problem behavior. Generalization across multiple therapists was demonstrated for both participants. However, generalization to another setting was not achieved for 1 participant until pairing was conducted in the second setting. Long-term maintenance was observed with 1 participant in the absence of further pairing trials. Maintenance via intermittent pairing trials was successful for the other participant.

Adult↗

Hyperactivity and spatial maze learning impairment of adult rats with temporary neonatal hypothyroidism.

Temporary hypothyroidism was induced in neonatal rats by 0.02% propylthiouracil (PTU) administration to lactating dams during days 0-19 after delivery, and its effects on the behavior and learning of their male offspring were examined. The serum T4 (thyroxine) level was returned to normal around 1 week after the last PTU administration, but the body weight gain was still depressed. The open field and Biel water maze tests at the age of 6 weeks showed an increased number of ambulations and an increase in errors with prolonged swimming time in the PTU rats. The radial arm maze test started at 13 weeks revealed that the PTU animals required more trials until they showed the first well-performed trial. The total number of choices was also larger, with less correct choices, and treatment effects on the response distribution and pattern were significant. Thus, the rats, which had suffered from temporary hypothyroidism in the neonatal period, showed hyperactivity and irreversible impairment in maze learning. These results suggest an involvement of temporary neonatal hypothyroidism in hippocampal dysfunction.

Animals↗

Bitonic dose-response functions for reinforcing and self-reported effects of nitrous oxide in humans.

The reinforcing and self-reported effects of nitrous oxide (10%, 30%, and 50% N(2)O in O(2)) were examined in 13 humans. During each of three sessions, subjects sampled one dose of N(2)O and 100% O(2) (placebo) for 10 min each, separated by 30-min recovery periods. The agents were identified by letter code, and later in the session, subjects chose nine times, once every 5 min, among N(2)O (e.g., "Agent A"), placebo (e.g., "Agent B"), or "neither" (also 100% O(2), identified as "drug-free air"). Self-reported and psychomotor effects were measured at various times. Dose-response functions varied across subjects and included bitonic, monotonic increasing, monotonic decreasing, U-shaped, and flat dose-response functions for reinforcing and/or self-reported effects. For subjects who showed bitonic reinforcing effects, the descending limb of the dose-response function could not be attributed to behavioral impairment. This study replicates previous studies showing dose-dependent effects of N(2)O, as well as between-subject variability in N(2)O effects. Bitonic dose-response functions for some subjects extend the generality of the phenomenon of bitonicity of drug effects to N(2)O effects in humans.

Adult↗

Age differences in behavior and PET activation reveal differences in interference resolution in verbal working memory.

Older adults were tested on a verbal working memory task that used the item-recognition paradigm. On some trials of this task, response-conflict was created by presenting test-items that were familiar but were not members of a current set of items stored in memory. These items required a negative response, but their familiarity biased subjects toward a positive response. Younger subjects show an interference effect on such trials, and this interference is accompanied by activation of a region of left lateral prefrontal cortex. However, there has been no evidence that the activation in this region is causally related to the interference that the subjects exhibit. In the present study, we demonstrate that older adults show more behavioral interference than younger subjects on this task, and they also show no reliable activation at the same lateral prefrontal site. This leads to the conclusion that this prefrontal site is functionally involved in mediating resolution among conflicting responses or among conflicting representations in working memory.

Aged↗

On the investigation of primed and chronic autonomous and heteronomous motivational orientations.

Four studies examined primed and chronic autonomous and heteronomous motivations. Study 1 showed that autonomy and heteronomy can be primed and influence perceptions and behavior in a way consistent with consciously regulated motives. In Study 2, a measure of chronic motivation was developed and its construct validity and reliability were assessed. In Study 3, the chronicity measure predicted behavior while consciously regulated motives predicted intention but not behavior. Results of Study 4 replicated results of the priming manipulation in Study 1. However, this effect was moderated by level of motivational chronicity. The priming effect was found to be stronger for non-chronics than for chronics. Overall, the findings suggest that autonomous and heteronomous motivations can be regulated automatically as well as consciously.

Achievement↗

Age differences in how consumers behave following exposure to DTC advertising.

This study was conducted to provide additional evidence on how consumers behave following direct-to-consumer (DTC) advertising exposure and to determine if there are differences in ad-prompted acts (drug inquiry and drug requests) between different age groups (i.e., older, mature, and younger adults). The results suggest that younger, mature, and older consumers are all moved to act by DTC drug ads, but that each age group behaves in different ways. Somewhat surprisingly, age was not predictive of ad-prompted behavior. DTC advertising was no more effective at moving older consumers to behave than their younger counterparts. These results suggest that age does not matter that much when it comes to the "moving power" of prescription drug advertising, even though research indicates that older consumers are more vulnerable to the persuasive effects of communication.

Advertising↗

[Genetic analysis of various behavioral and physiologic characteristics in hybrids between hypertensive and normotensive rats. Analysis of reciprocal differences].

As a result of reciprocal crosses between the SHR rats (spontaneously hypertensive strain) and WKY rats (normotensive strain), two types each of the F1 and F2 hybrids and 4 types of backcrosses were obtained. Analysis of reciprocal differences carries out in these generations for a number of behavioral and physiological traits demonstrated linkage of an hereditary factor affecting expression of potassium appetite with the Y-chromosome. The maternal effect contrary to the action of chromosomal hereditary factors was established for locomotor activity in the peripheral zone of open field. This maternal effect was manifested in the F1 and F2 generations, but not in backcrosses.

Animals↗

The volitional nature of the simplest reflex.

Recent studies suggest that none of the behaviors of the vertebrate CNS are fixed responses incapable of change. Even the simplest reflex of all, the two-neuron, monosynaptic spinal stretch reflex (SSR), undergoes adaptive change under appropriate circumstances. Operantly conditioned SSR change occurs gradually over days and weeks and is associated with a complex pattern of CNS plasticity at both spinal and supraspinal sites.

Animals↗

Laternal nicotine exposure increases nicotine preference in periadolescent male but not female C57B1/6J mice.

Maternal cigarette smoking is a risk factor for adolescent smoking. One possible explanation for increased smoking by human adolescents after maternal nicotine exposure is that exposure increases nicotine preference. However, it is difficult to separate the biological and social causes of smoking behavior in humans. This experiment examined the relationship between maternal nicotine exposure and nicotine preference in periadolescent offspring using a mouse model of oral nicotine consumption. Pregnant females were provided saccharin-flavored water containing 50 microg/ml nicotine (n = 4) or no nicotine (n = 5) from the ninth day of gestation through weaning on postnatal day (PD) 21. Offspring from these females were tested for nicotine preference during periadolescence (PDs 35-42) by providing access to both saccharin-only and nicotine solutions (50 microg/ml) 24 hr a day in the home cage in a two-bottle choice test. Male mice exposed maternally to nicotine (n = 9) exhibited an increased nicotine preference in adolescence compared to non-nicotine exposed controls (n = 12). Maternal nicotine exposure did not alter nicotine preference by periadolescent female mice. Nicotine consumption was confirmed by serum cotinine measurement. These data are consistent with human epidemiological reports that maternal nicotine exposure is associated with increased risk of cigarette smoking. Differential outcomes for males and females suggest that different processes underlie sex differences in nicotine consumption following maternal nicotine exposure.

Age Factors↗

Issues underlying prevalence of "doctor-shopping" behavior.

Data were collected on all persons within a sample of upper-and lower-income households who had seen physicians for illness episodes within a year prior to the interview. Forty-eight percent of upper-and 37 percent of lower-income families in the sample had changed doctors because of dissatisfaction with some aspect of the care. Factors related to tendency to shop for doctors in both upper-and lower-income groups were a lack of confidence in doctors' competence, unwillingness of doctors to spend time talking with patients, hostile feelings toward doctors, high cost of services, inconvenience of location and hours, and unfavorable attitudes toward doctors' personal qualities. Hypochondriasis was related to doctorshopping in the upper-income group. Results of this investigation suggest that patients may be becoming more discriminating in their choice of physicians.

Attitude↗

Brain mechanism of reward prediction under predictable and unpredictable environmental dynamics.

In learning goal-directed behaviors, an agent has to consider not only the reward given at each state but also the consequences of dynamic state transitions associated with action selection. To understand brain mechanisms for action learning under predictable and unpredictable environmental dynamics, we measured brain activities by functional magnetic resonance imaging (fMRI) during a Markov decision task with predictable and unpredictable state transitions. Whereas the striatum and orbitofrontal cortex (OFC) were significantly activated both under predictable and unpredictable state transition rules, the dorsolateral prefrontal cortex (DLPFC) was more strongly activated under predictable than under unpredictable state transition rules. We then modelled subjects' choice behaviours using a reinforcement learning model and a Bayesian estimation framework and found that the subjects took larger temporal discount factors under predictable state transition rules. Model-based analysis of fMRI data revealed different engagement of striatum in reward prediction under different state transition dynamics. The ventral striatum was involved in reward prediction under both unpredictable and predictable state transition rules, although the dorsal striatum was dominantly involved in reward prediction under predictable rules. These results suggest different learning systems in the cortico-striatum loops depending on the dynamics of the environment: the OFC-ventral striatum loop is involved in action learning based on the present state, while the DLPFC-dorsal striatum loop is involved in action learning based on predictable future states.

Brain↗

Routinization and emotional well-being: an experience sampling investigation in an elderly French sample.

This investigation examined the predictive validity of routinization preference measures, as well as the association of routinization to state affect in daily life. The authors collected naturalistic repeated observations from elderly participants living in private residences or retirement homes. Preferences for routinization were significantly associated with the repetition of both behaviors and environmental contexts. Routines were associated with decreases in positive affect in within-person analyses but had no association to anxious or depressed mood states. The findings are discussed in terms of the complexity of the routinization concept and its relevance for understanding emotional well-being in elderly people.

Activities of Daily Living↗

Individual differences in the priming effect of ethanol in social drinkers.

OBJECTIVE: Alcohol-dependent individuals frequently report increased desire for alcohol and exhibit increased alcohol-seeking behaviors following a single drink. The phenomenon, known as priming, has been demonstrated in the laboratory in alcohol-dependent humans and in nonhumans, but the effect is inconsistently observed in nonproblem social drinkers. The current experiment examined this effect in healthy, nonproblem social drinkers across a range of preload doses. METHOD: Using a repeated-measures design, 12 social drinkers were given ethanol (0.2, 0.4 or 0.8 g/kg) or placebo preloads. Various subjective effects measures were obtained at regular intervals. In addition, before and after consuming, the preload subjects performed an operant task on which they made repeated choices for either ethanol or money. RESULTS: Ethanol dose-dependently increased subjective reports of drug liking and desire to take more ethanol. When data from all subjects were examined, ethanol did not affect choices for ethanol on the choice task. However, in subjects who reported the greatest positive mood effects from ethanol (0.8 g/kg), the ethanol preload increased choices for ethanol over money on the choice task. CONCLUSIONS: These findings provide evidence for a priming effect of ethanol in social drinkers as measured by increased subjective desire for drug. The findings also suggest that the priming effects may be strongest in individuals who experience the greatest subjective positive mood effects from ethanol.

Adult↗

Unintended consequences of immigration reform: discrimination and Hispanic employment.

The record-keeping requirements of the Immigration Reform and Control Act(IRCA), and fines for illegal employment, may induce employers to discriminate against foreign-appearing workers. The General Accounting Office (GAO) reported widespread IRCA-related discrimination but did not link reported discriminatory practices to discriminatory employment behavior. We analyze the GAO's random survey and, controlling for selectivity effects, demonstrate that employers who report discriminatory practices actually employ fewer Hispanics. Although the measured reduction of Hispanic employment due to IRCA is fairly small, this finding parallels research alerting us to adverse consequences of a law that so far has achieved few of its intended effects.

Choice Behavior↗

Maternal experience influences the establishment of visual/auditory, but not olfactory recognition of the newborn lamb by ewes at parturition.

Maternal behavior in sheep is characterized by the rapid establishment of individual recognition of the lamb through the use of different sensory modalities. Olfactory recognition mediates acceptance at suckling whereas visual/auditory cues are involved in recognition from a distance. This study investigates (a) the timing of both types of recognition and (b) whether they can be influenced by maternal experience. Olfactory recognition was assessed at lambing, 30 min, 1, 2, or 4 hr postpartum by presenting successively an alien and the familiar lamb. Recognition at a distance was assessed at 6, 8, and 12 hr postpartum by using a two-choice test between the familiar and an alien lamb. A majority (33/51) of ewes showed selectivity at suckling as early as 30 min after parturition, and no differences due to maternal experience were observed. By contrast, in the two-choice recognition test, multiparous ewes showed a preference for their familiar lamb at 6 hr whereas primiparous mothers did so only after 24 hr of mother-young contact: The performance of biparous mothers was intermediate. Thus, both types of recognition can be rapidly established after parturition, and maternal experience has a differential effect on the dynamics of these learning processes.

Animals↗

Dexamethasone prevents long-lasting learning impairment following a combination of lipopolysaccharide and hypoxia-ischemia in neonatal rats.

OBJECTIVE: There are no established therapies for preventing or rescuing perinatal infection or inflammation-induced perinatal brain damage. We administered dexamethasone (DEX), a synthetic corticosteroid anti-inflammatory drug, to neonatal rats in a model of such damage induced by a combination of lipopolysaccharide (LPS) and hypoxia-ischemia (HI), which produces characteristic histologic and behavioral abnormalities. STUDY DESIGN: Four hours after the injection of LPS (1 mg/kg, i.p.), 7-day-old Wistar rat pups were subjected to unilateral HI for 1 hour according to Levine's procedure. Injections of 0.5 mg/kg of dexamethasone (DEX-treated group, n = 15) or saline (saline-treated group, n = 15) were given 4 hours before HI. A sham-operated control group received neither LPS nor HI (n = 15). We chose rats of this age because their stage of brain maturation is similar to the human neonate. Over the 7 to 16 weeks after treatment, a choice reaction time (CRT) task was used for assessment of attention processes in each group, an 8-arm radial maze task was used to test short-term memory, and a water maze task was used to test long-term memory. In the CRT task, the reward food was released when the tested animal correctly pressed a lever on the side of an illuminating lamp. The correct and incorrect lever pressings were counted. In the 8-arm radial maze task, rats were allowed to move freely, seeking a reward of food placed at the end of 1 arm. An error was defined as the choice of an arm that had already been visited. In the water maze, rats had to swim to seek a concealed platform as aversive escape motivation. At 19 weeks, the rats were euthanized, the brain was removed, sectioned coronally, and the volume of each part was measured. RESULTS: The striatum, cortex, and hippocampus showed reductions in volume in the saline-treated group (42.7%, 49.2%, and 34.9% decreases compared with the sham-operated controls, respectively), but this was not observed in the DEX-treated group. All learning and memory processes were impaired with the combination of LPS and HI treatment, but these deficits were almost completely prevented by DEX treatment. CONCLUSION: Dexamethasone is a promising candidate for prevention of infection and inflammation-induced perinatal brain damage. The impact of dexamethasone identifies potential therapeutic pathways once the mechanism of dexamethasone's protection is determined.

Animals↗